Study of Cetuximab With Radiation Followed by Consolidation Chemotherapy for NSCLC

Non Small Cell Lung Cancer (NSCLC) Clinical Trial

Official title:

A Phase II Study of Cetuximab in Combination With External Beam Radiation Followed By Consolidation Chemotherapy for Patients With Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00492206
• Other study ID #: UPCI 05-106
• Status: Completed
• Phase: Phase 2
• First received: June 26, 2007
• Last updated: January 16, 2013
• Start date: June 2006
• Est. completion date: February 2012

Study information

• Verified date: January 2013
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This is an open label, phase II study in which cetuximab with concurrent thoracic radiotherapy followed by consolidation chemotherapy with paclitaxel/carboplatin/cetuximab will be administered to subjects with locally advanced NSCLC.

Description:

This is a Phase II study to determine the overall survival for patients with locally advanced NSCLC treated with cetuximab with concurrent thoracic radiotherapy followed by consolidation chemotherapy with paclitaxel/carboplatin/cetuximab. This is a multicenter study including 36 subjects who will be males and females, both greater than 18 years of age. All subjects will initially receive radiation and cetuximab. Radiation will be given once a day (Monday-Friday) for approximately 6-8 weeks. During the course of radiation, cetuximab will be given intravenously once a week. Approximately 4-6 weeks after the last radiation dose, the subjects will be treated with chemotherapy, paclitaxel/carboplatin. Chemotherapy will be given intravenously once every 3 weeks for 3 cycles (1 cycle=3 weeks). Cetuximab intravenous administration will be continued throughout the entire study, once a week through week 26 including during chemotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed diagnosis of non-small cell lung cancer

• Patients must have surgically unresectable stage IIIA disease or stage IIIB disease without malignant pleural/pericardial effusion

• Patients must have measurable disease as per the RECIST criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See section 9.2 for the evaluation of measurable disease.

• Age >18 years. Lung cancer is extremely rare in children.

• ECOG performance status 0-1 (Karnofsky >70%; see Appendix A).

• If available, tumor tissue should be submitted for EGFR status by IHC and correlative studies.

• Patients must have normal organ and marrow function as defined below:

• leukocytes >3,000/µL

• absolute neutrophil count >1,500/µL

• platelets >100,000/µL

• total bilirubin within normal institutional limits

• AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal

• creatinine within normal institutional limits OR

• creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal

• The effects of cetuximab on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because EGFR inhibitors, chemotherapeutic agents and radiation therapy, as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

• Patients must either be not of child bearing potential or have a negative pregnancy test within 7 days of treatment. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.

• Willingness to sign an approved informed consent.

Exclusion Criteria:

• Patients should not have received prior chest radiation therapy.

• Patients with a history of pulmonary fibrosis are excluded from study.

• Patients may not be receiving any other investigational agents.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin, paclitaxel, cetuximab or other agents used in the study.

• History of any cancer other than NSCLC (except non-melanoma skin cancer or carcinoma in situ of the cervix) within the last five years.

• Prior therapy with known specific inhibitors of the EGFR.

• History of severe allergic reaction to prior therapy with monoclonal antibodies

• Peripheral neuropathy of more than grade 1 in severity

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, significant history of uncontrolled cardiac disease ie. uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure,and cardiomyopathy with decreased ejection fraction, or psychiatric illness/social situations that would limit compliance with study requirements.

• Pregnant women are excluded from this study because carboplatin, paclitaxel, cetuximab and radiation therapy have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the above agents, breastfeeding should be discontinued if the mother is treated with the agents used in this study. These potential risks may also apply to other agents used in this study.

• Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. Therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with carboplatin, paclitaxel and cetuximab or other agents administered during the study. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.

• Active hepatitis.

• History of pulmonary fibrosis.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer (NSCLC)

Intervention

Drug:
• Cetuximab
The initial dose of cetuximab is 400 mg/m2 intravenously administered over 120 minutes, followed by weekly infusions at 250 mg/m2 IV over 60 minutes. Subjects will receive cetuximab from week 0 through week 26.

Locations

Country	Name	City	State
United States	Emory Winship Cancer Institute	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at John Hopkins	Baltimore	Maryland
United States	UPMC Cancer Center -Beaver	Beaver	Pennsylvania
United States	UPMC Cancer Center - Clairton	Clairton	Pennsylvania
United States	UPMC Cancer Center - Oakbrook Commons	Greensburg	Pennsylvania
United States	UPMC Cancer Center -Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Penn State Cancer Institute, Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	UPMC Cancer Center -Indiana	Indiana	Pennsylvania
United States	UPMC Cancer Center -John P. Murtha Pavilion	Johnstown	Pennsylvania
United States	UPMC Cancer Center -McKeesport	McKeesport	Pennsylvania
United States	Sylvester Comprehensive Cancer Center, University of Miami	Miami	Florida
United States	UPMC Cancer Center -Haymaker Rd.	Monroeville	Pennsylvania
United States	UPMC Cancer Center -Mosside Blvd.	Monroeville	Pennsylvania
United States	UPMC Cancer Center -Sewickley Medical Center	Moon Township	Pennsylvania
United States	UPMC Cancer Center -Mt. Pleasant	Mt. Pleasant	Pennsylvania
United States	UPMC Cancer Center -Jameson	New Castle	Pennsylvania
United States	UPMC Cancer Center -New Castle	New Castle	Pennsylvania
United States	Universtity of Pittsburgh Cancer Institute -Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center -Delafield Rd.	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center -Drake	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center -Passavant	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center -St. Clair	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center -St. Margaret	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center -UPMC Shadyside	Pittsburgh	Pennsylvania
United States	UPMC Presbyterian -Radiation Oncology	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center -UPMC Northwest	Seneca	Pennsylvania
United States	UPMC Cancer Center -Teramana Cancer Center	Steubenville	Ohio
United States	UPMC Cancer Center -Robert Eberly Pavilion	Uniontown	Pennsylvania
United States	UPMC Cancer Center -Uniontown	Uniontown	Pennsylvania
United States	UPMC Cancer Center -Washington	Washington	Pennsylvania
United States	UPMC Cancer Center -Wexford	Wexford	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pittsburgh	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the response rate with cetuximab and concurrent thoracic radiotherapy for patients with locally advanced NSCLC		approx. 5 years	Yes
Secondary	To determine the progression free survival		5 years	No
Secondary	To evaluate the safety of the treatment regimen		approx. 6-8 months	Yes
Secondary	To conduct correlative science studies on the baseline tumor tissue to evaluate for EGFR mutations and Akt, p-Akt, and MAPKinase		approx. 5 years	No